Urothelial lesions in Chinese-herb nephropathy

Rapidly progressive renal fibrosis after a slimming regimen including Chine se herbs containing aristolochic acid (AA) has been identified as Chinese-h erb nephropathy (CHN). We reported urothelial atypia in three patients with CHN, with the subsequent development in one patient of overt transitional cell carcinoma (ICC), Therefore, it was decided to remove the native kidney s, as well as the ureters, in all patients with CHN, Nineteen kidneys and u reters removed during and/or after renal transplantation from 10 patients w ere studied to assess critically urothelial lesions and to characterize the cellular expression of p53, a tumor-suppressor gene overexpressed in sever al types of malignancies. Multifocal high-grade flat TCC in situ (carcinoma in situ; CIS) was observed, mainly in the upper urinary tract, in four pat ients, a prevalence of 40%. In one of those patients, a superficially invas ive flat TCC of the right upper ureter, as well as two additional foci of n oninvasive papillary TCC, were found in the right pelvis and left lower ure ter, respectively. This patient also presented recurrent noninvasive papill ary TCC of the bladder. Furthermore, in all cases, multifocal, overall mode rate atypia was found in the medullary collecting ducts, pelvis, and ureter , All CIS and papillary TCC, as well as urothelial atypia, overexpressed p5 3, These results show that the intake of Chinese herbs containing AA has a dramatic carcinogenic effect. Carcinogenesis is associated with the overexp ression of p53, which suggests a role for a p53 gene mutation. The relation ship of this mutation with the reported presence of AA DNA adducts in the k idney remains to be explored. (C) 1999 by the National Kidney Foundation, I nc.